Stagewise decline in the activity of brain protein synthesis factors and relationship between this decline and longevity in two rodent species

Castañeda, M.; Vargas, Rocio; Galvan, Silvia

doi:10.1016/0047-6374(86)90020-5

Cited by 13 publications

(6 citation statements)

References 26 publications

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“…Overall, the results presented herein suggest that the diminished rate of protein synthesis in brain during aging may have a multifactorial etiology. It seems likely that the decrease in RNA and eIF-2 concentrations and the fall in eIF-2B activity reported in the present study, in combination with the decrease in eIF-2 and eEF-1 activities reported elsewhere [5], may all play a role in the decremental changes in protein synthesis that occur in brain during aging. Finally, the large decrease in eIF-2 activity in brain of old versus young rats is not due to a decrease in eIF-2 concentration and is probably not due to a decrease in eIF-2B activity.…”

Section: -supporting

confidence: 63%

“…In addition, the rate of protein synthesis was significantly lower (P < 0.05) in spleen from 4month-old than in 1-month-old animals. Since eIF-2 activity is significantly decreased in liver [11] and brain [4][5][6] during aging, and because a decrease in eIF-2B activity could cause a decrease in eIF-2 activity measured in tissue extracts, eIF-2B activity was measured in postmitochondrial extracts from liver and brain. The activity of eIF-2B in extracts from brain was only approx.…”

Section: -mentioning

confidence: 99%

“…The efficiency of translation can be regulated through alterations in the activity ofpeptide-chain initiation and/or elongation factors. For example, the activities of both eIF-2 and eukaryotic elongation factor 1 (eEF-1) decrease in rat and mouse brain with increasing age [5]. However, in brain, polysomal aggregation diminishes with age [32,33].…”

Section: -mentioning

confidence: 99%

“…The mechanism involved in the age-dependent decrease in protein synthesis in brain is unknown. However, recent studies have shown that the activity of eukaryotic initiation factor 2 (eIF-2) decreases in both rat and mouse brain in parallel with the decrease in the rate of protein synthesis [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

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Age-dependent decrease in the amount of eukaryotic initiation factor 2 in various rat tissues

Kimball

Vary

Jefferson

1992

Biochemical Journal

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Recent studies have suggested that the decline in protein synthesis that occurs in rat liver and brain during development and aging is associated with a decrease in the activity of eukaryotic initiation factor 2 (eIF-2). One way in which eIF-2 activity could be decreased in tissue extracts would be through a decrease in the activity of the GDP exchange factor, eIF-2B. In the present study, the activity of eIF-2B was measured in tissue extracts and was found to be less in older than in younger rats. Thus a decrease in eIF-2B activity could account for part of the decrease in protein synthesis that occurs during aging. Another way in which eIF-2 activity could be decreased would be through a decrease in amount of the protein. Therefore the amount of eIF-2 in various tissues was quantified by protein immunoblot analysis. We found that the amount of eIF-2 relative to total protein tended to fall with increasing age. Furthermore, eIF-2 content was directly proportional to the rate of protein synthesis in the tissues examined. Finally, slot-blot analysis of polyadenylated RNA revealed no significant change in the relative abundance of eIF-2 alpha mRNA with age. The last-mentioned experiments suggest that the synthesis of eIF-2 may be regulated through changes in the deficiency of translation of eIF-2 alpha mRNA rather than through changes in gene transcription.

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Section: -supporting

confidence: 63%

Section: -mentioning

confidence: 99%

Section: -mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Age-dependent decrease in the amount of eukaryotic initiation factor 2 in various rat tissues

Kimball

Vary

Jefferson

1992

Biochemical Journal

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“…The decline in fractional synthesis rate (FSR) of proteins in tissues of rats as they age has been associated with a greater RTT (Khasigov and Nikolaev, 1987;Merry and Holehan, 1991) and eEF-1 abundance (Castañeda et al, 1986;Rattan et al, 1991). However, decreases in eIF-2 abundance (Castañeda et al, 1986;Kimball et al, 1992Kimball et al, , 2004 and polysome size (Murthy, 1966;Zomzely et al, 1971) provide evidence that initiation controls the declining FSR.…”

Section: Introductionmentioning

confidence: 99%

Protein elongation rates in tissues of growing and adult sheep1

Connors

Poppi

Cant

2008

Journal of Animal Science

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To identify the relative roles of translation initiation and elongation in the long term control of protein synthesis in ovine tissues, fractional synthesis rates (FSR) and ribosomal transit times (RTT) were measured in vivo in 24 ewe lambs at 3 levels of intake [maintenance (M), 1.5M, and 2M] and 8 mature ewes at 2M intake. After 17 to 25 d on treatment, animals were given an i.v. flooding dose of l-[ring-2,6-(3)H]phenylalanine and tissues were collected for analysis of radioactivity in free protein, total protein, and nascent ribosome-associated proteins. Ribosome transit time (the inverse of elongation rate) averaged 83, 393, 183, 241, 85, and 113 s for liver, duodenum, skin, rumen, semimembranosus, and LM, respectively. In response to an increased level of intake, protein FSR increased (P < 0.01) in all tissues except rumen and was attributed to greater translational efficiency. There was no effect (P > 0.50) of intake on RTT in these tissues, and the estimated proportion of ribosomes attached to and actively translating mRNA was increased (P < 0.07), indicating that an upregulation of initiation was responsible for the greater FSR. Mature ewes exhibited lower (P < 0.10) protein FSR in all tissues compared with lambs, which was related to a decline in the RNA:protein ratio in all tissues except for liver and duodenum. In all tissues but liver and semimembranosus, RTT increased (P < 0.10) with age. The lower elongation rate was not considered to have influenced the protein synthetic rate, but it caused an increase in the proportion of ribosomes actively translating mRNA. It is anticipated that this work will provide direction to future studies of the molecular mechanisms of chronic FSR control.

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Comparative Neurochemical Effects of Repeated Methyl Parathion or Chlorpyrifos Exposures in Neonatal and Adult Rats

Liu

Olivier

Pope

1999

Toxicology and Applied Pharmacology

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Stagewise decline in the activity of brain protein synthesis factors and relationship between this decline and longevity in two rodent species

Cited by 13 publications

References 26 publications

Age-dependent decrease in the amount of eukaryotic initiation factor 2 in various rat tissues

Age-dependent decrease in the amount of eukaryotic initiation factor 2 in various rat tissues

Protein elongation rates in tissues of growing and adult sheep1

Comparative Neurochemical Effects of Repeated Methyl Parathion or Chlorpyrifos Exposures in Neonatal and Adult Rats

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